Long Noncoding RNAs Regulate Gene Expression

Transcription of eukaryotic genomes produces many long RNA molecules that do not encode proteins. Called long noncoding RNAs (lncRNAs), these RNAs are typically over 100 nucleotides in length. Thousands of lncRNAs have been discovered in the last five years. The DNA that encodes them, along with other DNA of unknown function, has been called “the dark matter of the genome.”

Although the function of many lncRNAs is still unclear, there is increasing evidence that at least some play a role in controlling gene expression by affecting transcription. For example, lincRNA-p21 interacts with a protein called p53, a transcription factor that activates numerous genes, including genes involved in cell cycle control and cancer. By repressing p53, lincRNA-21 affects the transcription of hundreds of genes. Other lncRNAs modify chromatin structure. One of the best-studied is Xist RNA, which plays a central role in dosage compensation in mammalian cells (described in Chapter 4). Still other lncRNAs are complementary to mRNA sequences and function by base pairing with the mRNA and preventing translation or splicing. Evidence suggests that other lncRNAs bring about genomic imprinting (see Chapters 4 and 12).